{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:16Z","timestamp":1772160076224,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dilated cardiomyopathy (DCM) is a heart disease characterized by left ventricular dilatation and systolic dysfunction. In 30% of cases, pathogenic variants, essentially private to each patient, are identified in at least one of almost 50 reported genes. Thus, while costly, exons capture\u2010based Next Generation Sequencing (NGS) of a targeted gene panel appears as the best strategy to genetically diagnose DCM. Here, we report a NGS strategy applied to pools of 8 DNAs from DCM patients and validate its robustness for rare variants detection at 4\u2010fold reduced cost. Our pipeline uses Freebayes to detect variants with the expected 1\/16 allele frequency. From the whole set of detected rare variants in 96 pools we set the variants quality parameters optimizing true positives calling. When compared to simplex DNA sequencing in a shared subset of 50 DNAs, 96% of SNVs\/InsDel were accurately identified in pools. Extended to the 384 DNAs included in the study, we detected 100 variants (ACMG class 4 and 5), mostly in well\u2010known morbid gene causing DCM such as TTN, MYH7, FLNC, and TNNT2. To conclude, we report an original pool\u2010sequencing NGS method accurately detecting rare variants. This innovative approach is cost\u2010effective for genetic diagnostic in rare diseases.<\/jats:p>","DOI":"10.1111\/cge.14427","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T02:55:23Z","timestamp":1698720923000},"page":"185-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>DNA<\/scp>\n                    \u2010pools targeted\u2010sequencing as a robust cost\u2010effective method to detect rare variants: Application to dilated cardiomyopathy genetic diagnosis"],"prefix":"10.1111","volume":"105","author":[{"given":"Claire","family":"Perret","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Proust","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Esslinger","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-3385","authenticated-orcid":false,"given":"Flavie","family":"Ader","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"},{"name":"APHP, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique, Service de Biochimie M\u00e9tabolique H\u00f4pital Universitaire Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University of Heidelberg  Heidelberg Germany"},{"name":"DZHK (German Centre for Cardiovascular Research)  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Pruny","sequence":"additional","affiliation":[{"name":"APHP, Centre de R\u00e9f\u00e9rence Maladies Cardiaques H\u00e9r\u00e9ditaires H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Isnard","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"},{"name":"APHP, Cardiology Department Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-3005","authenticated-orcid":false,"given":"Pascale","family":"Richard","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"},{"name":"APHP, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique, Service de Biochimie M\u00e9tabolique H\u00f4pital Universitaire Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David\u2010Alexandre","family":"Tr\u00e9gou\u00ebt","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Charron","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"},{"name":"APHP, Centre de R\u00e9f\u00e9rence Maladies Cardiaques H\u00e9r\u00e9ditaires H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"},{"name":"APHP, Cardiology Department Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Cambien","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Villard","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR\u2010S1166, Research Unit on Cardiovascular and Metabolic Diseases  Paris France"},{"name":"ICAN Institute for Cardiometabolism and Nutrition  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv727"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40484-016-0064-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093455"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu301"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.053033"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2019.100464"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0039-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010134"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2021.05.010"}],"container-title":["Clinical 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